GABA receptor (GABAR) types C (GABACR) and A (GABAAR) are both GABA-gated chloride channels that are distinguished by their distinct competitive antagonist properties. The structural mechanism underlying these distinct properties is not well understood. In this study, using previously identified binding residues as a guide, we made individual or combined mutations of nine binding residues in th...

Intracortical inhibition is crucial to proper functioning of the mature neocortex, yet, paradoxically, is reported to be rare or absent in the neonatal animal. We reexamined this issue by recording whole-cell postsynaptic currents (PSCs) of barrel cortex neurons in thalamocortical brain slices from neonatal mice. Monosynaptic, excitatory thalamocortical responses were elicited in layers V/VI ne...

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABAAR) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABAAR positive allosteric modulator, on seizure activity, ...

Cortical dysplasia is a developmental abnormality characterized by changes in the structure and function of the neocortex. This disorder is implicated in many neuropsychiatric disorders such as epilepsy, autism and schizophrenia, and results from failure of immature neurons to appropriately migrate to their cortical targets. We developed a model of cortical dysplasia by administering methylazox...

Carisoprodol is a frequently prescribed muscle relaxant. In recent years, this drug has been increasingly abused. The effects of carisoprodol have been attributed to its metabolite, meprobamate, a controlled substance that produces sedation via GABAA receptors (GABAARs). Given the structural similarities between carisoprodol and meprobamate, we used electrophysiological and behavioral approache...

GABAA receptor (R) positive allosteric modulators that selectively modulate GABAARs containing 2and/or 3over 1subunits have been reported across diverse chemotypes. Examples include loreclezole, mefenamic acid, tracazolate, and etifoxine. In general,“ 2/3-selective” GABAAR positive allosteric modulators are nonbenzodiazepines (nonBZs), do not show -subunit isoform selectivity, yet have anxiolyt...

Isoliquiritigenin (ILTG) is a chalcone compound and shows various pharmacological properties, including antioxidant and anti-inflammatory activities. In recent study, we have reported a novel role of ILTG in sleep through a positive allosteric modulation of gamma-aminobutyric acid type A (GABAA)-benzodiazepine (BZD) receptors. However, the effect of ILTG in GABAAR-mediated synaptic response in ...